Several lines of evidence now indicate that nerve growth factor isolated from mouse salivary glands displays multiple biologic functions which span several health-related functions. These activities include: 1) activation of plasminogen; 2) promotion of the rate of wound healing; 3) neurite outgrowth stimulatory activity; 4) activation of the classical pathway of complement; and 5) chemotactic activity toward human leukocytes. The research proposal contained herein is designed to enhance our understanding of each of these potential biologic roles of NGF. Experiments are designed to further our understanding of the chemical mechanism whereby NGF undergoes autocatalytic activation - and its control by zinc ion. Studies are also presented which aim to understand the isolation of NGF from Cohn Fraction III of human serum and from bovine seminal plasma. Finally, a major goal of the laboratory is to explore and to understand our recent finding that nerve growth factor is strongly chemotactic for polymorphonuclear leukocytes and for monocytes. These studies, together with our finding that NGF can participate directly in activation of the complement system, may contribute significantly to our understanding of the role of NGF in the wound healing process.